The proposed research career award is designed to develop the candidate's clinical research skills in order to prepare him for a career as an independent investigator in the application of functional brain imaging methods to the field of experimental therapeutics for neurodegenerative diseases. Research plan: Parkinson's disease (PD) and Huntington's disease (HD) may be viewed respectively as prototypic examples of degenerative hypokinetic and hyperkinetic movement disorders. Great strides have been made in the-understanding of the pathophysiological mechanisms underlying the neurodegenerative processes in both PD and HD, prompting clinical trials of new therapies aimed at slowing or halting the progression of these diseases. To assess these new therapies, reliable in vivo markers of neuronal loss are needed. Currently available clinical and functional measures of disease progression are relatively insensitive, and may not accurately reflect the extent of neuropathological change. Alternatively, quantitative biologically relevant brain imaging markers now exist which may be suitable as outcome measures for clinical trials. The goal of the proposed project is to assess the extent to which neurochemical and metabolic positron emission tomography (PET) imaging markers are sensitive to change in PD and HD, and to compare these measures to standard clinical indices of disease progression. We hypothesize that PET measures will be more sensitive to disease progression than clinical measures. If this is the case, clinical trials designed to assess potential neuroprotective therapies could require fewer patients and be completed in less time. Educational plan: By completing this project the candidate will gain extensive practical experience in functional brain imaging. In addition, the educational plan will focus on six main objectives: 1) The learning of PET imaging techniques; 2) The development of skills in brain network analysis and modeling; 3) The advancement of the candidate's knowledge of statistical methods; 4) The learning of the principals of functional magnetic resonance imaging (fMRI); 5) The development of the applicant's skills in laboratory management and supervision; and 6) The preparation of manuscripts and scientific presentations.